There was a relative lack of patient-reported outcome measures on functioning and medication side effects compared with patient-reported outcome measures on symptom burden and health-related quality of life.
Patient-reported outcomes and clinician-rate outcomes supplement each other and at most times support identical study conclusions. Future studies would benefit from a more systematic approach towards use of patient-reported outcomes and a clearer rationale of how to weigh and report the results in comparison with clinician-rated outcomes.
Patient-reported outcomes and clinician-rate outcomes supplement each other and at most times support identical study conclusions. Future studies would benefit from a more systematic approach towards use of patient-reported outcomes and a clearer rationale of how to weigh and report the results in comparison with clinician-rated outcomes.Cancer cells develop strong genetic dependencies, enabling survival under oncogenic stress. MYC is a key oncogene activated across most cancers, and identifying associated synthetic lethality or sickness can provide important clues about its activity and potential therapeutic strategies. On the basis of previously conducted genome-wide screenings in MCF10A cells expressing MYC fused to an estrogen receptor fragment, we identified UVSSA, a gene involved in transcription-coupled repair, whose knockdown or knockout decreased cell viability when combined with MYC expression. Synthetic sick interactions between MYC expression and UVSSA down-regulation correlated with ATM/CHK2 activation, suggesting increased genome instability. We show that the synthetic sick interaction is diminished by attenuating RNA polymerase II (RNAPII) activity; yet, it is independent of UV-induced damage repair, suggesting that UVSSA has a critical function in regulating RNAPII in the absence of exogenous DNA damage. Supporting this hypothesis, RNAPII ChIP-seq revealed that MYC-dependent increases in RNAPII promoter occupancy are reduced or abrogated by UVSSA knockdown, suggesting that UVSSA influences RNAPII dynamics during MYC-dependent transcription. Taken together, our data show that the UVSSA complex has a significant function in supporting MYC-dependent RNAPII dynamics and maintaining cell survival during MYC addiction. While the role of UVSSA in regulating RNAPII has been documented thus far only in the context of UV-induced DNA damage repair, we propose that its activity is also required to cope with transcriptional changes induced by oncogene activation.DNA double-strand breaks (DSBs) are mainly repaired by c-NHEJ and HR pathways. The enhanced DSB mobility after DNA damage is critical for efficient DSB repair. Although microtubule dynamics have been shown to regulate DSB mobility, the reverse effect of DSBs to microtubule dynamics remains elusive. Here, we uncovered a novel DSB-induced microtubule dynamics stress response (DMSR), which promotes DSB mobility and facilitates c-NHEJ repair. DMSR is accompanied by interphase centrosome maturation, which occurs in a DNA-PK-AKT-dependent manner. Depletion of PCM proteins attenuates DMSR and the mobility of DSBs, resulting in delayed c-NHEJ. Remarkably, DMSR occurs only in G1 or G0 cells and lasts around 6 h. Both inhibition of DNA-PK and depletion of 53BP1 abolish DMSR. Taken together, our study reveals a positive DNA repair mechanism in G1 or G0 cells in which DSBs actively promote microtubule dynamics and facilitate the c-NHEJ process.How chromatin bridges are relayed to the chromosomal passenger complex (CPC) during mammalian cell division is unknown. In this issue, Petsalaki and Zachos (2020. J. Cell Biol.https//doi.org/10.1083/jcb.202008029) show that the DNA damage checkpoint kinases ATM and Chk2 signal to the CPC to associate with a pool of cytoskeletal regulators, MKLP2-Cep55, in the midbody center and to delay abscission.To prospectively evaluate whether diabetic macular ischemia detected with coherence tomography angiography (OCTA) is associated with change in functional outcomes over a period of one year.
This is a one-year prospective, observational study that included 56 eyes with varying levels of diabetic retinopathy. All participants underwent best corrected visual acuity evaluation, swept-source OCTA and microperimetry at baseline and repeated at one year. Parafoveal vessel densities (VD) and foveal avascular zone (FAZ) areas were generated from OCTA in the superficial and deep vascular plexuses. The influence of baseline and change in OCTA parameters on change in visual acuity and retinal sensitivity over one year was evaluated.
Over the one-year follow-up period, 16% (9) of eyes had at least one line worsening in BCVA and 7% (4) of eyes had at least 5% decrease in retinal sensitivity compared to baseline. Diabetic retinopathy progressed in 12.5%. https://www.selleckchem.com/products/az-33.html Mean superficial vascular plexus (SVP) FAZ area increased (0.32 ger decreases in SVP VD were associated with worsening of retinal sensitivity over a course of one year in diabetic individuals.Family health history is important to clinical care and precision medicine. Prior studies show gaps in data collected from patient surveys and electronic health records (EHRs). The All of Us Research Program collects family history from participants via surveys and EHRs. This Demonstration Project aims to evaluate availability of family health history information within the publicly available data from All of Us and to characterize the data from both sources.
Surveys were completed by participants on an electronic portal. EHR data was mapped to the Observational Medical Outcomes Partnership data model. We used descriptive statistics to perform exploratory analysis of the data, including evaluating a list of medically actionable genetic disorders. We performed a subanalysis on participants who had both survey and EHR data.
There were 54872 participants with family history data. Of those, 26% had EHR data only, 63% had survey only, and 10.5% had data from both sources. There were 35217 participants with reported family history of a medically actionable genetic disorder (9% from EHR only, 89% from surveys, and 2% from both). In the subanalysis, we found inconsistencies between the surveys and EHRs. More details came from surveys. When both mentioned a similar disease, the source of truth was unclear.
Compiling data from both surveys and EHR can provide a more comprehensive source for family health history, but informatics challenges and opportunities exist. Access to more complete understanding of a person's family health history may provide opportunities for precision medicine.
Compiling data from both surveys and EHR can provide a more comprehensive source for family health history, but informatics challenges and opportunities exist. Access to more complete understanding of a person's family health history may provide opportunities for precision medicine.